MPR1_YEASX
ID MPR1_YEASX Reviewed; 229 AA.
AC E9P8D2;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=N-acetyltransferase MPR1;
DE EC=2.3.1.271;
DE AltName: Full=(S)-1-pyrroline-5-carboxylate acetyltransferase;
DE AltName: Full=L-azetidine-2-carboxylate acetyltransferase;
DE Short=AZC acetyltransferase;
DE AltName: Full=Sigma1278b gene for proline-analog resistance 1;
GN Name=MPR1 {ECO:0000303|PubMed:10894734};
OS Saccharomyces cerevisiae (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=4932;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-85.
RC STRAIN=Sigma 1278B;
RX PubMed=10894734; DOI=10.1128/jb.182.15.4249-4256.2000;
RA Takagi H., Shichiri M., Takemura M., Mohri M., Nakamori S.;
RT "Saccharomyces cerevisiae sigma 1278b has novel genes of the N-
RT acetyltransferase gene superfamily required for L-proline analogue
RT resistance.";
RL J. Bacteriol. 182:4249-4256(2000).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-145; GLY-146;
RP GLN-147; LYS-148; VAL-149 AND GLY-150.
RX PubMed=11555637; DOI=10.1074/jbc.c100487200;
RA Shichiri M., Hoshikawa C., Nakamori S., Takagi H.;
RT "A novel acetyltransferase found in Saccharomyces cerevisiae Sigma1278b
RT that detoxifies a proline analogue, azetidine-2-carboxylic acid.";
RL J. Biol. Chem. 276:41998-42002(2001).
RN [3]
RP FUNCTION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12761200; DOI=10.1093/jb/mvg003;
RA Nomura M., Nakamori S., Takagi H.;
RT "Characterization of novel acetyltransferases found in budding and fission
RT yeasts that detoxify a proline analogue, azetidine-2-carboxylic acid.";
RL J. Biochem. 133:67-74(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15308773; DOI=10.1073/pnas.0403349101;
RA Nomura M., Takagi H.;
RT "Role of the yeast acetyltransferase Mpr1 in oxidative stress: regulation
RT of oxygen reactive species caused by a toxic proline catabolism
RT intermediate.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12616-12621(2004).
RN [5]
RP FUNCTION.
RX PubMed=20550582; DOI=10.1111/j.1567-1364.2010.00650.x;
RA Nishimura A., Kotani T., Sasano Y., Takagi H.;
RT "An antioxidative mechanism mediated by the yeast N-acetyltransferase Mpr1:
RT oxidative stress-induced arginine synthesis and its physiological role.";
RL FEMS Yeast Res. 10:687-698(2010).
RN [6]
RP FUNCTION.
RX PubMed=22698729; DOI=10.1016/j.febslet.2012.05.056;
RA Nishimura A., Nasuno R., Takagi H.;
RT "The proline metabolism intermediate Delta1-pyrroline-5-carboxylate
RT directly inhibits the mitochondrial respiration in budding yeast.";
RL FEBS Lett. 586:2411-2416(2012).
RN [7] {ECO:0007744|PDB:3W6S, ECO:0007744|PDB:3W6X, ECO:0007744|PDB:3W91}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND
RP SUBSTRATE, SUBUNIT, AND MUTAGENESIS OF ASN-135 AND ASN-178.
RX PubMed=23818613; DOI=10.1073/pnas.1300558110;
RA Nasuno R., Hirano Y., Itoh T., Hakoshima T., Hibi T., Takagi H.;
RT "Structural and functional analysis of the yeast N-acetyltransferase Mpr1
RT involved in oxidative stress tolerance via proline metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:11821-11826(2013).
CC -!- FUNCTION: N-acetyltransferase involved in oxidative stress resistance.
CC Acetylates the toxic proline metabolism intermediate (S)-1-pyrroline-5-
CC carboxylate (P5C), or more likely its spontaneously forming tautomer
CC glutamate-5-semialdehyde (GSA) into N-acetyl-GSA for arginine synthesis
CC in the mitochondria. P5C has been shown to increase the levels of
CC reactive oxigen species (ROS) in the cell by inhibiting the function of
CC the respiratory chain in the mitochondria. The enzyme is able to reduce
CC intracellular ROS levels under P5C-induced oxidative stress and
CC protects cells from damage by oxidative stress (PubMed:15308773,
CC PubMed:20550582, PubMed:22698729). Also acetylates and thereby
CC detoxifies the proline analog azetidine-2-carboxylate (AZC), however it
CC is unlikely that AZC is a natural substrate as it occurs only in plants
CC belonging to the Lilaceae family (PubMed:11555637). Does not acetylate
CC proline (PubMed:11555637, PubMed:12761200).
CC {ECO:0000269|PubMed:11555637, ECO:0000269|PubMed:12761200,
CC ECO:0000269|PubMed:15308773, ECO:0000269|PubMed:20550582,
CC ECO:0000269|PubMed:22698729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-glutamate 5-semialdehyde = CoA + H(+) + N-
CC acetyl-L-glutamate 5-semialdehyde; Xref=Rhea:RHEA:48232,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29123, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:58066; EC=2.3.1.271;
CC Evidence={ECO:0000269|PubMed:15308773};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20.9 mM for azetidine-2-carboxylate {ECO:0000269|PubMed:23818613};
CC KM=0.9 mM for azetidine-2-carboxylate {ECO:0000269|PubMed:15308773};
CC KM=7.019 mM for (S)-1-pyrroline-5-carboxylate
CC {ECO:0000269|PubMed:15308773};
CC KM=4.3 mM for acetyl-CoA {ECO:0000269|PubMed:23818613};
CC Note=kcat is 17.9 sec(-1) with azetidine-2-carboxylate as substrate
CC and 121 sec(-1) with (S)-1-pyrroline-5-carboxylate as substrate.
CC {ECO:0000269|PubMed:15308773};
CC pH dependence:
CC Optimum pH is 8.5-9 for azetidine-2-carboxylate and 6.5-7 for (S)-1-
CC pyrroline-5-carboxylate. {ECO:0000269|PubMed:12761200,
CC ECO:0000269|PubMed:15308773};
CC Temperature dependence:
CC Optimum temperature is 35 degrees Celsius.
CC {ECO:0000269|PubMed:12761200};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12761200,
CC ECO:0000269|PubMed:23818613}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11555637,
CC ECO:0000269|PubMed:20550582}. Mitochondrion
CC {ECO:0000269|PubMed:20550582}.
CC -!- PTM: Not glycosylated. {ECO:0000269|PubMed:11555637}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB031349; BAA95611.1; -; Genomic_DNA.
DR PDB; 3W6S; X-ray; 1.90 A; A/B/C=1-229.
DR PDB; 3W6X; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-229.
DR PDB; 3W91; X-ray; 2.10 A; A/B/C=1-229.
DR PDBsum; 3W6S; -.
DR PDBsum; 3W6X; -.
DR PDBsum; 3W91; -.
DR AlphaFoldDB; E9P8D2; -.
DR SMR; E9P8D2; -.
DR EnsemblFungi; KZV11534; KZV11534; WN66_01978.
DR KEGG; ag:BAA95611; -.
DR SGD; S000029666; MPR1.
DR VEuPathDB; FungiDB:YJL127C; -.
DR BioCyc; MetaCyc:MON-20450; -.
DR BRENDA; 2.3.1.271; 984.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR SUPFAM; SSF55729; SSF55729; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Mitochondrion; Transferase.
FT CHAIN 1..229
FT /note="N-acetyltransferase MPR1"
FT /id="PRO_0000446015"
FT DOMAIN 65..219
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 135
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23818613,
FT ECO:0007744|PDB:3W6X"
FT BINDING 145..150
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000305|PubMed:11555637"
FT BINDING 172..173
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23818613,
FT ECO:0007744|PDB:3W6X"
FT VARIANT 85
FT /note="G -> E (in allele MPR2)"
FT /evidence="ECO:0000269|PubMed:10894734"
FT MUTAGEN 135
FT /note="N->A: Increases the KM for AZC 20-fold."
FT /evidence="ECO:0000269|PubMed:23818613"
FT MUTAGEN 135
FT /note="N->D: Abolishes AZC acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23818613"
FT MUTAGEN 145
FT /note="R->A: Abolishes acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 146
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 147
FT /note="Q->A: No effect."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 148
FT /note="K->A,G: No effect."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 149
FT /note="V->A: Abolishes acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 150
FT /note="G->A: Abolishes acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11555637"
FT MUTAGEN 178
FT /note="N->A: Causes a 40-fold reduction in the apparent
FT kcat value."
FT /evidence="ECO:0000269|PubMed:23818613"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 41..49
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 55..71
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 92..100
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 116..127
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 149..160
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 168..175
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:3W6S"
FT TURN 184..189
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 191..200
FT /evidence="ECO:0007829|PDB:3W6S"
FT STRAND 209..217
FT /evidence="ECO:0007829|PDB:3W6S"
FT HELIX 223..226
FT /evidence="ECO:0007829|PDB:3W6S"
SQ SEQUENCE 229 AA; 26233 MW; CE6110904DE2D665 CRC64;
MDAESIEWKL TANLRNGPTF FQPLADSIEP LQFKLIGSDT VATAFPVFDT KYIPDSLINY
LFKLFNLEIE SGKTYPQLHS LTKQGFLNYW FHSFAVVVLQ TDEKFIQDNQ DWNSVLLGTF
YIKPNYAPRC SHNCNAGFLV NGAHRGQKVG YRLAQVYLNW APLLGYKYSI FNLVFVTNQA
SWKIWDKLNF QRIGLVPHAG ILNGFSEPVD AIIYGKDLTK IEPEFLSME
